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Review
. 2018 Nov 8;10(11):426.
doi: 10.3390/cancers10110426.

NF-κB Signaling in Targeting Tumor Cells by Oncolytic Viruses-Therapeutic Perspectives

Justyna Struzik  1 , Lidia Szulc-Dąbrowska  2
Affiliations
Review

NF-κB Signaling in Targeting Tumor Cells by Oncolytic Viruses-Therapeutic Perspectives

Justyna Struzik et al. Cancers (Basel). .

Abstract

In recent years, oncolytic virotherapy became a promising therapeutic approach, leading to the introduction of a novel generation of anticancer drugs. However, despite evoking an antitumor response, introducing an oncolytic virus (OV) to the patient is still inefficient to overcome both tumor protective mechanisms and the limitation of viral replication by the host. In cancer treatment, nuclear factor (NF)-κB has been extensively studied among important therapeutic targets. The pleiotropic nature of NF-κB transcription factor includes its involvement in immunity and tumorigenesis. Therefore, in many types of cancer, aberrant activation of NF-κB can be observed. At the same time, the activity of NF-κB can be modified by OVs, which trigger an immune response and modulate NF-κB signaling. Due to the limitation of a monotherapy exploiting OVs only, the antitumor effect can be enhanced by combining OV with NF-κB-modulating drugs. This review describes the influence of OVs on NF-κB activation in tumor cells showing NF-κB signaling as an important aspect, which should be taken into consideration when targeting tumor cells by OVs.

Keywords: NF-κB signaling; immunotherapy; oncolytic viruses.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Canonical and non-canonical nuclear factor (NF)-κB signaling. Activation and inhibition of NF-κB signaling components are indicated by pointing and blunt arrows, respectively. BAFF-R, B cell-activating factor receptor; BCR, B-cell receptor; CD30, cluster of differentiation 30; CD40, cluster of differentiation 40; c-IAP1, cellular inhibitor of apoptosis protein-1; c-IAP2, cellular inhibitor of apoptosis protein-2; IKKα, inhibitor of κB kinase α; IKKβ, inhibitor of κB kinase β; IKKγ, inhibitor of κB kinase γ; IκB, inhibitor of κB; LTβR, lymphotoxin-β receptor; NIK, nuclear factor-κB-inducing kinase; P, phosphate group; RANK, receptor activator of nuclear factor-κB; TAK1, transforming growth factor-β-activated kinase 1; TCR, T-cell receptor; TLRs, Toll-like receptors; TNF-α, tumor necrosis factor-α; TRAF2, tumor necrosis factor receptor-associated factor 2; TRAF3, tumor necrosis factor receptor-associated factor 3; TWEAK, tumor necrosis factor-like weak inducer of apoptosis; Ub-ubiquitin moieties.
Figure 2
Figure 2
The impact of oncolytic DNA viruses on nuclear factor (NF)-κB signaling. Activation of NF-κB signaling components is indicated by pointing black arrows. Inhibition of NF-κB is indicated by red blunt arrows. The outcomes of NF-κB modulation are shown in the brackets. Induction is indicated by green triangles, whereas inhibition—by inverted red triangles. 5-FC, 5-fluorocytosine; AV, adenovirus; CCL2, chemokine (C-C motif) ligand 2 gene; CpG, cytosine:guanine islands; CXCL8, C-X-C motif chemokine ligand 8 gene; HSV-1, herpes simplex virus type 1; IRAK4, interleukin-1 receptor–associated kinase 4; MyD88, myeloid differentiation primary response protein 88; PV, parvovirus; TLR9, Toll-like receptor 9; TRAF6, tumor necrosis factor receptor-associated factor 6; TSA, trichostatin A; UPAR, urokinase-type plasminogen activator receptor promoter.
Figure 3
Figure 3
Modulation of nuclear factor (NF)-κB signaling by oncolytic RNA viruses. Pointing black arrows indicate activation of NF-κB signaling components, whereas red blunt arrows indicate NF-κB inhibition. The effects of therapeutic agents on NF-κB are shown in the brackets. Green triangles represent induction, whereas inverted red triangles indicate inhibition. Ac, acetyl group; ActD, actinomycin-D; CDKN1A, cyclin-dependent kinase inhibitor 1 gene; c-Fos, cellular oncogene Fos; EMCV, encephalomyocarditis virus; Epac1, exchange protein directly activated by cyclic adenosine monophosphate isoform 1; Etp, etoposide; IFN-β, interferon-β; IKKα, inhibitor of κB kinase α; IKKβ, inhibitor of κB kinase β; IKKγ, inhibitor of κB kinase γ; IκB, inhibitor of κB; NDV, Newcastle disease virus; P, phosphate group; p38-MAPK, p38 mitogen-activated protein kinase; RSV, respiratory syncytial virus; RV, reovirus; Ub, ubiquitin moieties; VSV, vesicular stomatitis virus.
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